The first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages
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In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was a breakthrough in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another. https://www.youtube.com/embed/cisOFfBPZk0?wmode=transparent&start=0 The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.
Champions of xenotransplantation regard it as the solution to organ shortages across the world. In December 2023, 1,445 people in Australia were on the waiting list for donor kidneys. In the United States, more than 89,000 are waiting for kidneys.
One biotech CEO says gene-edited pigs promise “an unlimited supply of transplantable organs”.
Not, everyone, though, is convinced transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.
There are two critical barriers to the procedure’s success: organ rejection and the transmission of animal viruses to recipients.
But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.
What is CRISPR?
CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery allows them to integrate and ultimately destroy viral DNA by cutting it.
In 2012, two teams of scientists discovered how to harness this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins.
When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could program the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site.
In 2020, the two scientists leading these teams were awarded a Nobel prize for their work.
In the case of the latest xenotransplantation, CRISPR technology was used to edit 69 genes in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes. https://www.youtube.com/embed/UKbrwPL3wXE?wmode=transparent&start=0 How does CRISPR work?
A busy time for gene-edited xenotransplantation
While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.
In 2022 and 2023, two patients with terminal heart diseases, who were ineligible for traditional heart transplants, were granted regulatory permission to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures.
Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a clinically dead man (with family consent). The liver functioned well up until the ten-day limit of the trial.
How is this latest example different?
The gene-edited pig kidney was transplanted into a relatively young, living, legally competent and consenting adult.
The total number of gene edits edits made to the donor pig is very high. The researchers report making 69 edits to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.
Clearly, the race to transform these organs into viable products for transplantation is ramping up.
From biotech dream to clinical reality
Only a few months ago, CRISPR gene editing made its debut in mainstream medicine.
In November, drug regulators in the United Kingdom and US approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease.
The treatment, known as Casgevy, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the unhealthy gene that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape.
Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.
We’ll be talking more about gene-editing
Medicine and gene technology regulators are increasingly asked to approve new experimental trials using gene editing and CRISPR.
However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.
For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to early-stage embryonic cells in vitro (in the lab).
In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying 15 years’ imprisonment.
No jurisdiction in the world has laws that expressly permits heritable human genome editing. However, some countries lack specific regulations about the procedure.
Is this the future?
Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.
For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting beyond seven months.
While authorisation for this recent US transplant has been granted under the so-called “compassionate use” exemption, conventional clinical trials of pig-human xenotransplantation have yet to commence.
But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval in the US or elsewhere.
By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem some way off.
Christopher Rudge, Law lecturer, University of Sydney
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Common Hospital Blood Pressure Mistake (Don’t Let This Happen To You Or A Loved One)
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There’s a major issue in healthcare, Dr. Suneel Dhand tells us, pertaining to the overtreatment of hypertension in hospitals. Here’s how to watch out for it and know when to question it:
Under pressure
When patients, particularly from older generations, are admitted to the hospital, their blood pressure often fluctuates due to illness, dehydration, and other factors. Despite this, they are often continued on their usual blood pressure medications, which can lead to dangerously low blood pressure.
Why does this happen? The problem arises from rigid protocols that dictate stopping blood pressure medication only if systolic pressure is below a certain threshold, often 100. However, Dr. Dhand argues that 100 is already low*, and administering medication when blood pressure is close to this can cause it to drop dangerously lower
*10almonds note: low for an adult, anyway, and especially for an older adult. To be clear: it’s not a bad thing! That is the average systolic blood pressure of a healthy teenager and it’s usually the opposite of a problem if we have that when older (indeed, this very healthy writer’s blood pressure averages 100/70, and suffice it to say, it’s been a long time since I was a teenager). But it does mean that we definitely don’t want to take medications to artificially lower it from there.
Low blood pressure from overtreatment can lead to severe consequences, requiring emergency interventions to stabilize the patient.
Dr. Dhand’s advice for patients and families is:
- Ensure medication accuracy: make sure the medical team knows the correct blood pressure medications and dosages for you or your loved one.
- Monitor vital signs: actively check blood pressure readings, especially if they are in the low 100s or even 110s, and discuss any medication concerns with the medical team.
- Watch for symptoms of low blood pressure: be alert for symptoms like dizziness or weakness, which could indicate dangerously low blood pressure.
For more on all of this, enjoy:
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Want to learn more?
You might also like to read:
The Insider’s Guide To Making Hospital As Comfortable As Possible
Take care!
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Missing Microbes – by Dr. Martin Blaser
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You probably know that antibiotic resistance is a problem, but you might not realize just what a many-headed beast antibiotic overuse is.
From growing antibiotic superbugs, to killing the friendly bacteria that normally keep pathogens down to harmless numbers (resulting in death of the host, as the pathogens multiply unopposed), to multiple levels of dangers in antibiotic overuse in the farming of animals, this book is scary enough that you might want to save it for Halloween.
But, Dr. Blaser does not argue against antibiotic use when it’s necessary; many people are alive because of antibiotics—he himself recovered from typhoid because of such.
The style of the book is narrative, but information-dense. It does not succumb to undue sensationalization, but it’s also far from being a dry textbook.
Bottom line: if you’d like to understand the real problems caused by antibiotics, and how we can combat that beyond merely “try not to take them unnecessarily”, this book is very worthy reading.
Click here to check out Missing Microbes, and learn more about yours!
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Oat Milk vs Almond Milk – Which is Healthier?
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Our Verdict
When comparing oat milk to almond milk, we picked the almond milk.
Why?
This one’s quite straightforward, and no, it’s not just our bias for almonds
Rather, almonds contain a lot more vitamins and minerals, all of which usually make it into the milk.
Oat milk is still a fine choice though, and has a very high soluble fiber content, which is great for your heart.
Just make sure you get versions without added sugar or other unpleasantries! You can always make your own at home, too.
You can read a bit more about the pros and cons of various plant milks here:
Enjoy!
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If you’re worried about inflammation, stop stressing about seed oils and focus on the basics
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You’ve probably seen recent claims online seed oils are “toxic” and cause inflammation, cancer, diabetes and heart disease. But what does the research say?
Overall, if you’re worried about inflammation, cancer, diabetes and heart disease there are probably more important things to worry about than seed oils.
They may or may not play a role in inflammation (the research picture is mixed). What we do know, however, is that a high-quality diet rich in unprocessed whole foods (fruits, vegetables, nuts, seeds, grains and lean meats) is the number one thing you can to do reduce inflammation and your risk of developing diseases.
Rather than focusing on seed oils specifically, reduce your intake of processed foods more broadly and focus on eating fresh foods. So don’t stress out too much about using a bit of seed oils in your cooking if you are generally focused on all the right things.
What are seed oils?
Seed oils are made from whole seeds, such as sunflower seeds, flax seeds, chia seeds and sesame seeds. These seeds are processed to extract oil.
The most common seed oils found at grocery stores include sesame oil, canola oil, sunflower oil, flaxseed oil, corn oil, grapeseed oil and soybean oil.
Seed oils are generally affordable, easy to find and suitable for many dishes and cuisines as they often have a high smoke point.
However, most people consume seed oils in larger amounts through processed foods such as biscuits, cakes, chips, muesli bars, muffins, dipping sauces, deep-fried foods, salad dressings and margarines.
These processed foods are “discretionary”, meaning they’re OK to have occasionally. But they are not considered necessary for a healthy diet, nor recommended in our national dietary guidelines, the Australian Guide for Healthy Eating.
Seed oils often have a high smoke point.
Gleb Usovich/ShutterstockI’ve heard people say seed oils ‘promote inflammation’. Is that true?
There are two essential types of omega fatty acids: omega-3 and omega-6. These are crucial for bodily functions, and we must get them through our diet since our bodies cannot produce them.
While all oils contain varying levels of fatty acids, some argue an excessive intake of a specific omega-6 fatty acid in seed oils called “linoleic acid” may contribute to inflammation in the body.
There is some evidence linoleic acid can be converted to arachidonic acid in the body and this may play a role in inflammation. However, other research doesn’t support the idea reducing dietary linoleic acid affects the amount of arachidonic acid in your body. The research picture is not clear cut.
But if you’re keen to reduce inflammation, the best thing you can do is aim for a healthy diet that is:
- high in antioxidants (found in fruits and vegetables)
- high in “healthy”, unsaturated fatty acids (found in fatty fish, some nuts and olive oil, for example)
high in fibre (found in carrots, cauliflower, broccoli and leafy greens) and prebiotics (found in onions, leeks, asparagus, garlic and legumes)
low in processed foods.
If reducing inflammation is your goal, it’s probably more meaningful to focus on these basics than on occasional use of seed oils.
Choose foods high in fibre (like many vegetables) and prebiotics (like legumes).
Kiian Oksana/ShutterstockWhat about seed oils and heart disease, cancer or diabetes risk?
Some popular arguments against seed oils come from data from single studies on this topic. Often these are observational studies where researchers do not make changes to people’s diet or lifestyle.
To get a clearer picture, we should look at meta-analyses, where scientists combine all the data available on a topic. This helps us get a better overall view of what’s going on.
A 2022 meta-analysis of randomised controlled trials investigated the relationship between supplementation with omega-6 fatty acid (often found in seed oils) and cardiovascular disease risk (meaning disease relating to the heart and blood vessels).
The researchers found omega-6 intake did not affect the risk for cardiovascular disease or death but that further research is needed for firm conclusions. Similar findings were observed in a 2019 review on this topic.
The World Health Organization published a review and meta-analysis in 2022 of observational studies (considered lower quality evidence compared to randomised controlled trials) on this topic.
They looked at omega-6 intake and risk of death, cardiovascular disease, breast cancer, mental health conditions and type 2 diabetes. The findings show both advantages and disadvantages of consuming omega-6.
The findings reported that, overall, higher intakes of omega-6 were associated with a 9% reduced risk of dying (data from nine studies) but a 31% increased risk of postmenopausal breast cancer (data from six studies).
One of the key findings from this review was about the ratio of omega-3 fatty acids to omega-6 fatty acids. A higher omega 6:3 ratio was associated with a greater risk of cognitive decline and ulcerative colitis (an inflammatory bowel condition).
A higher omega 3:6 ratio was linked to a 26% reduced risk of depression. These mixed outcomes may be a cause of confusion among health-conscious consumers about the health impact of seed oils.
Overall, the evidence suggests that a high intake of omega-6 fatty acids from seed oils is unlikely to increase your risk of death and disease.
However, more high-quality intervention research is needed.
The importance of increasing your omega-3 fatty acids
On top of the mixed outcomes, there is clear evidence increasing the intake of omega-3 fatty acids (often found in foods such as fatty fish and walnuts) is beneficial for health.
While some seed oils contain small amounts of omega-3s, they are not typically considered rich sources.
Flaxseed oil is an exception and is one of the few seed oils that is notably high in alpha-linolenic acid (sometimes shortened to ALA), an omega-3 fatty acid.
If you are looking to increase your omega-3 intake, it’s better to focus on other sources such as fatty fish (salmon, mackerel, sardines), chia seeds, hemp seeds, walnuts, and algae-based supplements. These foods are known for their higher omega-3 content compared to seed oils.
The bottom line
At the end of the day, it’s probably OK to include small quantities of seed oils in your diet, as long as you are mostly focused on eating fresh, unprocessed foods.
The best way to reduce your risk of inflammation, heart disease, cancer or diabetes is not to focus so much on seed oils but rather on doing your best to follow the Australian Guide for Healthy Eating.
Lauren Ball, Professor of Community Health and Wellbeing, The University of Queensland and Emily Burch, Lecturer, Southern Cross University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Eat to Live – by Dr. Joel Fuhrman
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It sure would be great if we could eat all that we wanted, and remain healthy without putting on weight.
That’s the main intent of Dr. Joel Fuhrman’s book, with some caveats:
- His diet plan gives unlimited amounts of some foods, while restricting others
- With a focus on nutrient density, he puts beans and legumes into the “eat as much as you want” category, and grains (including whole grains) into the “restrict” category
This latter is understandable for a weight-loss diet (as the book’s subtitle promises). The question then is: will it be sustainable?
Current scientific consensus holds for “whole grains are good and an important part of diet”. It does seem fair that beans and legumes should be able to replace grains, for grains’ carbohydrates and fiber.
However, now comes the double-edged aspect: beans and legumes contain more protein than grains. So, we’ll feel fuller sooner, and stay fuller for longer. This means we’ll probably lose weight, and keep losing weight. Or at least: losing fat. Muscle mass will stay or go depending on what you’re doing with your muscles.
If you want to keep your body fat percentage at a certain level and not go below it, you may well need to reintroduce grains to your diet, which isn’t something that Dr. Fuhrman covers in this book.
Bottom line: this is a good, science-based approach for healthily losing weight (specifically, fat) and keeping it off. It might be a little too good at this for some people though.
Click here to check out Eat To Live and decide what point you want to stop losing weight at!
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Revive and Maintain Metabolism
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It’s Q&A Day at 10almonds!
Have a question or a request? You can always hit “reply” to any of our emails, or use the feedback widget at the bottom!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small
❝How to jump start a inactive metabolism and keep it going? THANKYOU❞
The good news is, if you’re alive, your metabolism is active (it never stops!). So, it may just need perking up a little.
As for keeping it going, well, that’s what we’re here for! We’re all in favor of healthy longevity.
We’ll do a main feature soon on what we can do to influence our metabolism in either direction, but to give some quick notes here:
- A lot of our metabolism is influenced by genes and is unalterable (without modifying our genes, anyway)
- Metabolism isn’t just one thing—it’s many. And sometimes, parts of our metabolism can be much quicker or slower than others.
- When people talk about wanting a “faster metabolism”, they’re usually referring to fat-burning, and that’s just a small part of the picture, but we understand that it’s a focal point for many.
There really is enough material for a whole main feature on metabolic tweaks, though, so watch this space!
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